RUBCN

Chr 3AR

rubicon autophagy regulator

Also known as: KIAA0226, RUBICON, SCAR15

NCBI Gene: 9711ENSG00000145016UniProt: Q92622

The protein encoded by this gene is a negative regulator of autophagy and endocytic trafficking and controls endosome maturation. This protein contains two conserved domains, an N-terminal RUN domain and a C-terminal DUF4206 domain. The RUN domain is involved in Ras-like GTPase signaling, and the DUF4206 domain contains a diacylglycerol (DAG) binding-like motif. Mutation in this gene results in deletion of the DAG binding-like motif and causes a recessive ataxia. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Apr 2014]

Primary Disease Associations & Inheritance

Spinocerebellar ataxia, autosomal recessive 15MIM #615705
AR
300
ClinVar variants
49
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— RUBCN
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
49 Pathogenic / Likely Pathogenic· 176 VUS of 300 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.79LOEUF
pLI 0.000
Z-score 2.78
OE 0.58 (0.43–0.79)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.47Z-score
OE missense 0.83 (0.77–0.89)
472 obs / 570.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.58 (0.43–0.79)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.77–0.89)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.92
0≤1.21.6
LoF obs/exp: 29 / 50.3Missense obs/exp: 472 / 570.7Syn Z: 0.98

ClinVar Variant Classifications

300 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic44
Likely Pathogenic5
VUS176
Likely Benign51
Benign17
Conflicting7
44
Pathogenic
5
Likely Pathogenic
176
VUS
51
Likely Benign
17
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
42
0
44
Likely Pathogenic
3
0
2
0
5
VUS
4
148
24
0
176
Likely Benign
0
14
11
26
51
Benign
0
7
1
9
17
Conflicting
—7
Total91698035300

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RUBCN · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

RUBCN-related syndromic intellectual disability with ataxia, dysarthria and epilepsy

limited
ARUndeterminedUncertain
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Spinocerebellar ataxia, autosomal recessive 15

MIM #615705

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Autozygome and high throughput confirmation of disease genes candidacy.
Maddirevula S et al.·Genet Med
2019
Metabolic effects of RUBCN/Rubicon deficiency in kidney proximal tubular epithelial cells.
Matsuda J et al.·Autophagy
2020
Clinical application of RUBCN/SESN2 mediated inhibition of autophagy as biomarkers of diabetic kidney disease.
Watany MM et al.·Mol Med
2022
A second RUBCN variant associated with epileptic encephalopathy and neurodevelopmental delay.
Magalie LP et al.·Am J Med Genet A
2025Case report
RUBCN as a novel prognostic biomarker and therapeutic target in breast cancer.
Yang DD et al.·PLoS One
2026
Ancient founder mutation in RUBCN: a second unrelated family confirms Salih ataxia (SCAR15).
Seidahmed MZ et al.·BMC Neurol
2020Case report
MIR144* inhibits antimicrobial responses against Mycobacterium tuberculosis in human monocytes and macrophages by targeting the autophagy protein DRAM2.
Kim JK et al.·Autophagy
2017
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Rare DisordersUndiagnosed DisordersDisorders of Unknown Prevalence

Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford

RECRUITING
NCT01793168Sanford HealthStarted 2010-07

External Resources

Links to major genomics databases and tools